{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:55:12Z","timestamp":1772117712360,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["For U1193"],"award-info":[{"award-number":["For U1193"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012958","name":"Minist\u00e8re de l'Education Nationale, de la Formation professionnelle, de l'Enseignement Sup\u00e9rieur et de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>\n                    Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and aggressive liver cancer with limited therapeutic options. Precise classification and immunotherapy are perspectives to improve the treatments. We reported the role of septin 9 in apico\u2010basal polarity and epithelial\u2010to\u2010mesenchymal transition (EMT). Here, we aim to elucidate its role in iCCA. We analyzed single\u2010cell transcriptomes from human iCCA tumor cells based on phenotype and cell state. Knockdown of the septin 9 gene (\n                    <jats:italic>SEPT9<\/jats:italic>\n                    ) was done using small interfering RNA (siRNA); interferon\u2010\u03b3 (IFN\u2010\u03b3) stimulation was performed using different CCA cells; gene expressions were analyzed by reverse transcription and real\u2010time PCR analysis (RT\u2010qPCR); and immunofluorescence, immunoblotting, and flow cytometry were performed to assess the expression of proteins. The differential distributions of\n                    <jats:italic>SEPT9<\/jats:italic>\n                    and vimentin (\n                    <jats:italic>VIM<\/jats:italic>\n                    ) gene expressions allowed us to define specific cellular trajectories of malignant cells and thus identified distinct clusters of iCCA cells. One cluster was enriched in\n                    <jats:italic>VIM<\/jats:italic>\n                    and extracellular\u2010matrix (ECM) remodeling molecules, and another had high expression of\n                    <jats:italic>SEPT9<\/jats:italic>\n                    and genes from the \u2018don't eat me\u2019 signal involved in immune escape. This antagonism between\n                    <jats:italic>SEPT9<\/jats:italic>\n                    and\n                    <jats:italic>VIM<\/jats:italic>\n                    was confirmed by\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments. Notably,\n                    <jats:italic>SEPT9<\/jats:italic>\n                    and \u2018don't eat me\u2019 gene expressions were inversely correlated to those of vimentin and the EMT markers.\n                    <jats:italic>SEPT9<\/jats:italic>\n                    expression was upregulated by IFN\u2010\u03b3 and\n                    <jats:italic>SEPT9<\/jats:italic>\n                    knockdown decreased expression of \u2018don't eat me\u2019 signal genes and increased expression of mesenchymal markers. Cancer Cell Line Encyclopedia (CCLE) transcriptome database analyses confirmed that iCCA cells enriched in septin 9 exhibit epithelial\u2010like features. This study revealed septin 9 as a cytoskeleton element of iCCA epithelial\u2010like cells and a regulator of the immune system response. It also brings new insights into the enigmatic relationship between EMT and immune response. Notably, we decoded a potential mechanism that could sensitize patients to immunotherapies.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13673","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T11:34:56Z","timestamp":1722425696000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Septin 9 expression regulates \u2018don't eat me\u2019 signals and identifies an immune\u2013epithelial class of intrahepatic cholangiocarcinoma"],"prefix":"10.1002","author":[{"given":"Ting ting","family":"Cai","sequence":"first","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Desterke","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, UFR M\u00e9decine\u2010INSERM UMR1310  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Peng","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Agnetti","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peixuan","family":"Song","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalila","family":"Ouazib","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Guettier","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Samuel","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"},{"name":"AP\u2010HP H\u00f4pital Paul Brousse, Centre H\u00e9pato\u2010Biliaire AP\u2010HP H\u00f4pital Paul\u2010Brousse, Centre H\u00e9pato\u2010Biliaire  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9878-7811","authenticated-orcid":false,"given":"Ama","family":"Gassama\u2010Diagne","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 1193  Villejuif France"},{"name":"Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay, UMR\u2010S 1193 Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris Saclay, UMR\u2010S 1193  Villejuif France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(13)61903\u20100"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.007"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.026"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.11.048"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.028"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.09.010"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31410"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4810"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.04.007"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.57.070188.003113"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cws052"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.891281"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.000026"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096860"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)64262\u20109"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.07.004"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S36213"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010017\u20100004\u2010z"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101456\u20100"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22396"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.045"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605\u2010007\u20100091\u20105"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2018.10.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1817931"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1807315"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18173"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010021\u201001625\u2010x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2011.072"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00122"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v12.i6.619"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2015.07.004"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27707"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.3024"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12203"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.02.015"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010800180\u20106.00007\u20104"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104288"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12141815"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.08.007"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp427"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24559"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102012\u2010304351"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201106131"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11\u201003\u20100253"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20109057\u20103_8"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7100147"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm863"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13384"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2021.101162"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129139"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.10.057"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051424"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1936"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.21450"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22815"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.314179"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.107094"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97611"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201021\u20104370"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.10.013"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010021\u201000781\u20104"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.13673","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T11:35:00Z","timestamp":1722425700000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.13673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,31]]},"references-count":64,"alternative-id":["10.1002\/1878-0261.13673"],"URL":"https:\/\/doi.org\/10.1002\/1878-0261.13673","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/1878-0261.13673\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.13673\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.13673\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.13673\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,31]]},"assertion":[{"value":"2024-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1878-0261.13673"}}